Comparison Between Mirtazapine and Megestrol for the Control of Anorexia-cachexia in Cancer Patients in Palliative Care.

NCT03283488 | Completed Phase 2

• 1 other identifier: Mirtazapine_Cachexia
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Cancer-associated anorexia-cachexia is an insidious syndrome that has a major impact on the patient's quality of life, but is also associated with a significant reduction in survival. Despite its clinical importance, it remains a widely underestimated and untreated condition. Considering the scarcity of pharmacological measures, it is necessary to invest in studies that may contribute to the rational and effective treatment of this clinical condition. Mirtazapine has a special therapeutic potential because it is a well-tolerated drug with few adverse effects and with well-known orexigenic action in clinical practice.The objective of this study is to evaluate the effect of mirtazapine as a pharmacological measure in the management of cancer-related anorexia-cachexia in patients in palliative care. A randomized, double-blind clinical trial involving 52 cancer patients with anorexia-cachexia in palliative care will be conducted. Patients will be randomized to receive mirtazapine or megestrol and will be evaluated longitudinally for a period of 8 weeks. The primary endpoint will be to assess the effect of mirtazapine on anorexia and weight gain and secondary outcomes will be to assess the tolerability and safety of mirtazapine and the effect of mirtazapine on body composition, quality of life, and functional capacity of patients.

Conditions

Cachexia; Cancer; Anorexia

Keywords

anorexia; cachexia; mirtazapine; megestrol; palliative care

Outcome Measures

Primary Outcomes (2)

• Change in appetite

  Assessed by Edmonton Symptom Assessment Scale. This evaluation will be collected at baseline and after 8 weeks of follow-up. Changes in appetite will be divided into 3 categories according to the following definitions: appetite improvement will be a decrease ≥ 2 points in Edmonton Symptom Assessment Scale, maintenance of appetite as an improvement or worsening of 1 point and worsening of appetite as deterioration ≥ 2 points.

  8 weeks

• Change in body weight

  Assessed by body weight. This evaluation will be collected at baseline and after 8 weeks of follow-up. The weight changes will be divided into 3 categories according to the following definitions: weight improvement will be a gain ≥ 1 kg, weight maintenance will be a loss \< 500g or a gain \< 1kg and weight loss will be a loss ≥ 500g.

  8 weeks

Secondary Outcomes (6)

• Change in body lean and fat mass

  8 weeks

• Change in Quality of life

  8 weeks

• Assessment of muscle strength

  8 weeks

• Assessment of gait speed

  8 weeks

• Physical Activity behaviour

  8 weeks

Study Arms (2)

Mirtazapine

EXPERIMENTAL

Tablets of 15mg mirtazapine will be used according to randomization. At the first visit, patients will be instructed to take one tablet at night for better tolerability. From the second week, if there is good tolerance, they will take two tablets at night until the end of the study.

Drug: Mirtazapine

Megestrol

ACTIVE COMPARATOR

Tablets of 160mg megestrol will be used according to randomization. At the first visit, patients will be instructed to take one tablet at night for better tolerability. From the second week, if there is good tolerance, they will take two tablets at night until the end of the study.

Drug: Megestrol

Interventions

Mirtazapine DRUG

Tablets of 15mg mirtazapine will be used according to randomization. At the first visit, patients will be instructed to take one tablet at night for better tolerability. From the second week, if there is good tolerance, they will take two tablets at night until the end of the study.

Also known as: Remeron

Mirtazapine

Megestrol DRUG

Tablets of 160mg megestrol will be used according to randomization. At the first visit, patients will be instructed to take one tablet at night for better tolerability. From the second week, if there is good tolerance, they will take two tablets at night until the end of the study.

Also known as: megestrol acetate

Megestrol

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥ 50 years.
• Patients with confirmed diagnosis of cancer by histopathological examination, including those not yet submitted to any therapy because they are in the therapeutic definition phase and those whose therapies have already been suspended because they are ineffective.
• Patients with cancer progression, with either local or distant metastases, documented by radiological or histopathological methods.
• Patients complaining of anorexia graded by the patient as ≥ 5 by the Edmonton Sympton Assessement Scale.
• Patients with weight loss ≥ 2% in the last 2 months or weight loss ≥ 5% in the last 6 months, referred by the patient or documented in electronic medical records, compared to the stable weight before diagnosis.
• Patients with a life expectancy of ≥ 2 months by the Palliative Prognostic Score.
• Patients with performance status greater than or equal to 60% using the Karnofsky Performance Status scale.

You may not qualify if:

• Patients diagnosed with depression or using antidepressant therapy with a score ≥ 12 in the depression items of the Hospital Anxiety and Depression Scale.
• Patients with unstable doses of corticosteroids.
• Patients with moderate renal and/or hepatic dysfunction (total bilirubin ≥ 1.5x the upper limit of normal, AST and ALT ≥ 5x upper limit of normal or creatinine ≥1.5x upper limit of normal).
• Patients with Central Nervous System metastases.
• Patients with inability to take oral medications.
• Patients with mechanical obstruction of the gastrointestinal tract.
• Patients with clinically bulky ascites and generalized edema.
• Patients with reports of allergy to the medications studied.
• Patients with hypothyroidism with TSH levels greater than or equal to 5 μU/mL and free T4 less than 0.7 ng/dL.
• Patients with uncorrected hydroelectrolytic disturbances, with altered serum sodium, potassium and/ or ionic calcium.
• Patients with persistent and uncontrolled nausea and/or vomiting associated with gastrointestinal tract neoplasia and/or chemotherapeutic or radiotherapeutic treatment.
• Patients with pacemakers.

Sponsors & Collaborators

• University of Sao Paulo: lead

Study Sites (1)

Clinics Hospital, Ribeirão Preto Medical School, University of São Paulo

Ribeirão Preto, São Paulo, 14048900, Brazil

Location

Related Publications (4)

• Riechelmann RP, Burman D, Tannock IF, Rodin G, Zimmermann C. Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Am J Hosp Palliat Care. 2010 Mar;27(2):106-10. doi: 10.1177/1049909109345685. Epub 2009 Sep 23.

  PMID: 19776373 BACKGROUND

• Theobald DE, Kirsh KL, Holtsclaw E, Donaghy K, Passik SD. An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms. J Pain Symptom Manage. 2002 May;23(5):442-7. doi: 10.1016/s0885-3924(02)00381-0.

  PMID: 12007762 BACKGROUND

• Tomiska M, Tomiskova M, Salajka F, Adam Z, Vorlicek J. Palliative treatment of cancer anorexia with oral suspension of megestrol acetate. Neoplasma. 2003;50(3):227-33.

  PMID: 12937858 BACKGROUND

• Wen HS, Li X, Cao YZ, Zhang CC, Yang F, Shi YM, Peng LM. Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy. 2012;58(6):461-7. doi: 10.1159/000346446. Epub 2013 Feb 7.

  PMID: 23406994 BACKGROUND

Related Links

• webpage of the Ribeirão Preto Medical School

MeSH Terms

Conditions

Cachexia; Neoplasms; Anorexia

Interventions

Mirtazapine; Megestrol; Megestrol Acetate

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Nereida KC Lima, MD, PhD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 10, 2017
• First Posted: September 14, 2017
• Study Start: March 26, 2019
• Primary Completion: February 2, 2022
• Study Completion: February 2, 2022
• Last Updated: July 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: after the publication of the results of study.
• Access Criteria: researchers after the review and approval of protocol by the principal investigator

Locations

BR (1)